New study sheds more light on estrogen/breast cancer link

To determine the relationship between estrogen use and the risk of invasive breast cancer, a group of Harvard-based medical researchers studied 28,800 post-menopausal women enrolled in the observational Nurses’ Health Study (NHS). They wanted to find out whether the long-term use of estrogen increased a woman’s chances of getting breast cancer and what part age and weight played in the outcome.

“Latest research showed no statistically significant increase in breast cancer risk in women who took estrogen only for up to 20 years.”

Their findings showed no statistically significant increase in breast cancer risk in women who took estrogen only for up to 20 years. However, after that point, breast cancer risk became statistically significant. The study was published May 8 in the Archives of Internal Medicine.

Approximately 4.4 million women in the United States use menopause hormones. Many take estrogen only. Around 900,000 take a combination of estrogen and progestin. A 2002 conducted by the Women’s Health Initiative (WHI) found that the combination of these two hormones increased breast cancer risk by 24 percent after five years. In a follow up study this year on “estrogen only” therapy, the WHI found no increase in breast cancer risk with usage up to 6.8 years.

Data covers 22-year period

The Nurses’ Health Study was established in 1976 with 121,700 female registered nurses age 30 to 55 years. Participants were predominately Caucasian and reflected the demographics of registered nurses. They completed a baseline questionnaire that included risk factors for cancer and cardiovascular disease.

The research team narrowed their group to women who had hysterectomies and were taking estrogen alone. From 1980 through 2002, researchers conducted follow-up questionnaires. All of the subjects used oral, unopposed conjugated estrogen. Most of them used the standard 0.625-mg. dose.

Study findings

Researchers analyzed 934 invasive breast cancers. They noted the risk of tumors that have hormone receptors for both estrogen and progesterone was increased in women who took estrogen for 15 years as compared to those who took it for 10 years or less. At 20 years, the risk of any type of breast cancer was increased by 42 percent.

Results were similar when the analysis was limited to:

• women who were 50 years old and had undergone a hysterectomy, regardless of their menopausal status;

• post-menopausal women of all age groups;

• women older than 60, and

• women who started estrogen after age 50.

One significant finding was that thin women who take hormones had a 77 percent greater risk for breast cancer than thin women who do not take hormones. Yet overweight women who used estrogen 20 years or more had only a 25 percent greater risk.

“Although current users (of estrogen) were younger, thinner and less likely to have a family history of breast cancer than never users, these factors would have led to a decreased risk of breast cancer in the current user group rather than the increased risk we observed,” the study authors wrote.

They note that while the short-term use of estrogen doesn’t appear to be associated with breast cancer risk, the WHI study showed that using the hormone for less than 10 years increased the risk of deep-vein thrombosis, and in women well past the menopausal transition, of stroke.

The researchers concluded that, “Women who take estrogen therapy for prevention or treatment of osteoporosis typically require longer-term treatment and should thus explore other options, given the increased risk of breast cancer with longer-term use.”

Alternative treatments

Sales of commercial prescription hormones have fallen dramatically since 2002 when the first health risks were reported by the WHI. Many women have turned to compounded estrogens and progestins, which use customized doses of plant-based hormones. Wyeth, the biggest seller of prescription menopause hormones, has asked the FDA to regulate the pharmacy-mixed hormones.

The FDA states that these hormones, also known as bioidentical drugs, carry similar health risks to commercially prescribed hormones. Before the bioidentical drugs are prescribed, a doctor performs a saliva test to determine the level of hormones in the woman’s body. Medical groups have expressed concern about the safety of these compounds. Doctors have also expressed skepticism about the validity of the saliva tests.

For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.

Page last updated: 2/9/2015 2:16:21 PM

What the news means for you

Estrogen use under 15 years appears less risky

Kathryn Dillon, MD, NCMPObstetrics and Gynecology

The Nurses Health Study corroborates the previous study by the Women’s Health Initiative, which showed no increase in breast cancer with estrogen usage up to 6.8 years. That was very surprising to many people. The nurses’ study, in my opinion, didn’t show significant risk until after 15-20 years.

I think it’s notable that the association between estrogen and breast cancer was clearer among leaner women, but that was still after they had taken estrogen more than 10 years. Taken globally, I think the study allows women to feel more comfortable taking estrogen up to 10 years.

There are some limitations to the study, however. The participants were a self-selected group of people. The study wasn’t randomized, placebo-controlled or double-blind. Also, most participants were on the standard dose of 0.625-mg. of estrogen. Is that to say that dose has the same risk as, for instance, the ultra-low dose Menostar patch, which is estrogen prescribed for osteoporosis prevention? I think that’s a big leap to make, but we do not know.

To put things in perspective, the relative risk of breast cancer is greatly influenced by family history. Having your first child after the age of 30 and hormone therapy are very low risk factors in comparison.

Cardiovascular risks

Looking at the bigger picture, breast cancers are still not the primary killers of women. Cardiovascular disease is. Further interpretation of the WHI and other studies indicates that, within the first 10 year after menopause, women who use hormones had significantly decreased cardiovascular disease. However, estrogen can increase the risk for heart disease within the first year in older women who already have atherosclerosis.

The data really isn’t hard enough yet for anyone to recommend that hormones be used as a preventive measure for cardiovascular disease. The American College of Obstetricians and Gynecologists and the North American Menopause Society (NAMS) restrict hormone use to symptom relief, with the lowest dose for the shortest period of time. But NAMS also adds "consistent with treatment goals, benefits and risks for the individual woman." This allows a little more latitude.

Talking with your doctor

When and why to take hormone therapy is a discussion that will take place between the doctor and the patient every year. It’s not a commitment for life. Generally, a woman who is uncomfortable with hot flashes, difficulty sleeping, night sweats or fractured sleep benefits from low-dose estrogen therapy. But it’s different with every patient. Her risks and family history have to be considered.

Usually women with menopausal symptoms feel so much better on estrogen. And most who start estrogen usually stop taking it on their own within the first year. Only about 25 percent continue.

Low doses can be administered with a transdermal patch, creams or gels. Other options are vaginal rings that are good for three months and dispense estrogen continuously. They’re very convenient. One is just for local symptoms, the others treat systemic symptoms and do not affect liver metabolism.

Compounded hormones

Compounded estrogens are a completely different subject. Women think they’re getting hormones as their body used to make them, or bioidentical hormones. The saliva test used to detect hormones and determine the dose is not a true, tested method. Saliva levels do not correlate to plasma levels of hormones. In the end, the pharmacist uses symptoms to determine the compounded mixture. Additionally, compounded hormones are not regulated by the FDA, and patients may assume they do not have the same risks as those made by a drug company, which isn’t the case.

Actually, physicians already have access to bioidentical hormones. The estradiol used through a patch, a cream and vaginal rings is bioidentical. The ovaries make estradiol, the predominant potent estrogen. Prometrium, a commonly prescribed progesterone drug, is also bioidentical.

Frequently, patients don’t want to talk to their doctor about options for hormone therapy. They already know what they want to do. I think the sensationalism around the WHI study struck fear into women about taking hormones. Now, three to four years later, with more information, we can reassure people about some of the risks and benefits.

Dr. Dillon is assistant professor of obstetrics and gynecology at the University of Kentucky College of Medicine.

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